The Crazies stars Timothy Olyphant and Radha Mitchell. The film takes place in the fictional town of Ogden Marsh, Pierce County, Iowa, "friendliest place on Earth," whose town water supply is accidentally infected with the "Trixie" virus. After an incubation period of 48 hours, this virus gradually transforms the mental state of the infected into that of cold, calculating, depraved, bloodthirsty killers, who then prey on family and neighbors alike.

The film was released on February 26, 2010 to positive reviews from critics, and was a modest box office success.

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In the town of Ogden Marsh, Iowa, David Dutten (Timothy Olyphant), the local sheriff, is enjoying a baseball game when it is interrupted by a local resident, Rory Hamill, who enters the outfield with a shotgun. David, knowing Rory's history of alcoholism, attempts to dissuade him, but is forced to kill him when he raises his weapon. David and his wife Judy (Radha Mitchell), the community doctor, begin to notice other town residents exhibiting bizarre behavior, including listlessness and repetitive speech. The next night, a local farmer burns his house down with his wife and son trapped inside. When firefighters arrive, he is found mowing his lawn while his house burns.

Learning of a pilot's body found in a swamp, David and his deputy Russell Clank (Joe Anderson) investigate it. They discover a military aircraft that crashed into the river a few days before, contaminating the drinking water. Suspecting a link to the town residents' odd behavior, David shuts off the town's water supply.

Soon after, communication services are lost in town, and soldiers arrive to take all residents to quarantine at the high school. Everyone is examined for symptoms of infection. Judy does not pass the examination and is separated from David. She explains her fever is due to pregnancy, but is sedated anyway. David escapes evacuation and heads back to his office, encountering Russell. The two head for the school to free Judy. At the school, the infected townspeople breach the perimeter, and the military personnel evacuate, abandoning the civilians. Judy wakes up strapped to a gurney, as a crazed school director kills quarantined people one by one. David and Russell save her in time, and also find Becca (Danielle Panabaker), a hospital assistant.

Unable to find a working vehicle, the four make their way out of town on foot. They encounter Becca's boyfriend, Scotty, at his farm. Soldiers raid the farm, shoot Scotty and his mother, and burn the bodies. They learn that the soldiers have been ordered to shoot all civilians who have potentially been exposed. The group repair an older patrol car in David's and Judy's garage, and are ambushed by the infected family of Rory. After a struggle, Russell furiously shoots the infected multiple times. This greatly disturbs Judy, who argues with David about Russell's state of mind. On the road, they are spotted by an attack helicopter and drive into a car wash for cover. The infected car wash workers attack and one drags Becca out of the car with a wrapped hose, breaking her neck. When the rest of the group leaves the car to help her, the helicopter destroys the car.

Russell disables a passing government SUV with a police spike strip. The driver reveals the cargo plane contained "Trixie," a "Rhabdoviridae prototype" biological weapon. It was en route to Texas to be destroyed when the plane crashed. Enraged, Russell shoots the driver and threatens Judy and David. When confronted about his behavior, Russell realizes he is infected and, after being disarmed, begs to go on with Judy and David. He later dies while distracting soldiers at a roadblock, so that Judy and David can sneak past.

David and Judy arrive at a truck stop to search for a vehicle, discovering that the military have also executed those who were evacuated. Fending off three infected, they escape in a semi-truck. Ogden Marsh is destroyed in a massive explosion as they flee, and their truck flips in the passing shockwave. As the couple walk towards Cedar Rapids, a view from a military satellite highlights first the couple, then the city, and the words "Initiate containment protocol" appear, signifying a new containment attempt.

In the credits, Bruce Aune, a real newscaster from KCRG-TV 9 in Cedar Rapids, Iowa reports that an explosion originating from the Dakon Pendrill chemical plant started a massive fire in Ogden Marsh. He says a perimeter has been set and civilians are not being allowed into the area. A Trixie-infected individual appears on camera just before the signal is lost.

The final stage of the Trixie disease took three hours in the make-up chair to complete.

The makeup for the film was designed by Almost Human Studios, who also did makeup for other horror films such as Quarantine, Frankenfish and Prom Night. Director Breck Eisner's first visions of what the infected would look like were zombies. He and the makeup crew made many molds and sketches of what the infected should look like, with deformities and skin hanging off and so forth. Eventually, he grew tired of the "zombie" look which he believed to be too cliché and decided to go for a more realistic "go under the skin," in which the blood vessels would appear to be bursting forth and face and neck muscles and tendons tight and wrought. Eisner described this look as "hyper alive."

The director's one and only rule for the makeup design was that they would have to research in medical books and consult medical professionals for the design of the infected. Lead make-up artist Rob Hall said "If we were to pitch something to Breck, about, if you know, one side of his face should look like this, Breck would immediately want to know what disease it came from, and what version of reality it could be implemented into Trixie. But the most important thing was to make sure it felt real. Make it feel like you could get it, too." The basis of the makeup the crew used was mainly rabies, tetanus and Stevens–Johnson syndrome.

Each "Crazy" design had about 21 separate pieces that took over three hours to apply for the final effect seen in the film. Robert stated the final effect in the film seen was not just the makeup, but the lighting, camera angles, and post-production effects were the main factor. The main theme for the design was "stress." He stated he wanted the "Crazies" to look stressed out. The veins and eyes were the main focus of the design. The contact lenses covered the actors' entire eyes and required eyedrops every five minutes to prevent permanent eye damage.[5]

The film premiered on February 24, 2010 in Los Angeles[6] and received a wide release in the North America on February 26, 2010.[7] The Canadian DVD and Blu-ray Disc were released June 29, 2010.[8] The DVD and Blu-ray Disc + Digital Copy combo pack was released in the North America on June 29, 2010 and in the UK on July 19.[9]

Reviews for the film have been generally positive. Based on 148 reviews collected by Rotten Tomatoes, the film has an overall approval rating of 71%, with an average score of 6.4/10. The site's consensus states the film is "Tense, nicely shot, and uncommonly intelligent, The Crazies is a horror remake that, unusually, works."[10] By contrast, Metacritic calculated a "mixed or average" score of 55% based on 30 reviews.[11]

Michael Phillips of The Chicago Tribune awarded the film 3½ stars of 4 commenting that he "greatly prefer this cleverly sustained and efficiently relentless remake to the '73 edition. It is lean and simple."[12] Eric M. Armstrong of The Moving Arts Film Journal wrote that "The Crazies is a solid B-movie and one of the few remakes that actually surpasses the original."[13]Ty Burr of The Boston Globe gave the film 3/4 stars touting the film as "extremely solid stuff – about as good as you could hope from a B-movie retread."[14]Variety film critic Dennis Harvey also praised the film, writing "While not a slam dunk, this revamp by helmer Breck Eisner (of the enjoyable but underperforming Sahara) emerges an above-average genre piece that's equal parts horror-meller and doomsday action thriller.[15]

However, Owen Gleiberman of Entertainment Weekly graded the film a C, writing, "I don't care how this premise has been dressed up, we've seen it a jillion times before."[16] Mike Hale of The New York Times wrote a mixed review stating "The filmmakers seem so determined to make a serious, respectable horror movie that they have only the bare minimum of fun."[17] Amy Biancolli, writing for San Francisco Chronicle, wrote that the remake "boasts less of the plot and fewer characters than the original, but the hairdos are spiffier and the special effects have graduated from cheapo stage blood to the extravagant gross-outs that horror audiences now routinely expect."[18]

In 2013, George A. Romero claimed he would enjoy making a sequel to The Crazies called "The Even Crazier". However, he said it was unlikely due to predictably poor reviews and an apparent lack of interest.